Development of T cell receptor repertoires during childhood in health and disease

By Emma A., Bunia A., Othilia FS., Tobias C. & Joanna R.

Group 21

Introduction

Based on the article Mitchell et al. (2022)
Allele repertoire development during childhood and type 1 diabetes
Two groups of patients, case and control
Returns four times for observations

Materials:

1. Data from immunoSEQ ANALYZER

Methods:

1. Base R
1. Tidyverse R
2. PCA analysis
3. MCA analysis

Data Description

Original data (01_dat_load.tsv)

[1] 359  12
# A tibble: 359 × 2
   sample_name sample_tags                                                      
   <chr>       <chr>                                                            
 1 310183_TCRB 06 Years, 6 Years at visit, Caucasian, Control, Control 022, GAD…
 2 310110_TCRB 0 Years at visit, 09 Months, 6.37808219178082 Years at diagnosis…
 3 310206_TCRB 0 Years at visit, 10 Months, 10.558904109589 Years at diagnosis,…
 4 310288_TCRB 09 Years, 9 Years at visit, 9.56986301369863 Years at diagnosis,…
 5 310271_TCRB 02 Years, 2 Years at visit, 6.87397260273973 Years at diagnosis,…
 6 310244_TCRB 05 Years, 18.0438356164384 Years at diagnosis, 5 Years at visit,…
 7 310137_TCRB 07 Years, 7 Years at visit, Caucasian, Control, Control 014, Fem…
 8 310258_TCRB 12 Years, 12 Years at visit, 12.958904109589 Years at diagnosis,…
 9 310127_TCRB 04 Years, 11.6821917808219 Years at diagnosis, 4 Years at visit,…
10 310300_TCRB 17 Years, 17 Years at visit, 17.7561643835616 Years at diagnosis…
# ℹ 349 more rows
[1] 10

Data Wrangling

Augmented data (03_dat_aug.tsv)

[1] 13824    24
# A tibble: 10 × 24
   sample_name total_templates productive_templates fraction_productive
   <chr>                 <dbl>                <dbl>               <dbl>
 1 310102_TCRB          121173                96410               0.796
 2 310102_TCRB          121173                96410               0.796
 3 310102_TCRB          121173                96410               0.796
 4 310102_TCRB          121173                96410               0.796
 5 310102_TCRB          121173                96410               0.796
 6 310102_TCRB          121173                96410               0.796
 7 310102_TCRB          121173                96410               0.796
 8 310102_TCRB          121173                96410               0.796
 9 310102_TCRB          121173                96410               0.796
10 310102_TCRB          121173                96410               0.796
# ℹ 20 more variables: total_rearrangements <dbl>,
#   productive_rearrangements <dbl>, productive_simpson_clonality <dbl>,
#   max_productive_frequency <dbl>, locus <chr>, sku <chr>, test_name <chr>,
#   case_control <chr>, id <dbl>, timepoint <dbl>, gender <chr>,
#   ethnicity <chr>, race <chr>, age <dbl>, age_diagnosis <dbl>,
#   age_visit <dbl>, antibody <chr>, expression <dbl>, allele <chr>,
#   subtype <chr>

Antibody Expression

Antibody Expression, PCA

HLA Expression

HLA Expression, PCA

Discussion

Discuss the implications of your findings. Interpret the results and relate them to your objectives.

Implications of findings

  • Patterns exist between the different mean antibody expressions. Suggests need for PCA. .
  • Two components explain majority of variance in data. Components are used to express the rotation matrix.
  • The rotation matrix shows the variance between the variables. Two clusters form between the four variables, each more strong associated with each of the two component.
  • The HLA analysis suggests alleles of interest, by indicating dominant subtypes in case subjects, compared to control.
  • MCA…

Limitations

  • Missing values for control subjects

Conclusion

  • Clear differences exist between case and control subjects, both in terms of antibody expression and in terms of allele subtypes.
  • Suggests that both antibody expression and allele subtype are involved in the development of diabetes in children.
  • Based on our results, HLA-DQB1*0202, HLA-B*4402, HLA-A*2402, and HLA-B*0702 could have a direct influence on type 1 diabetes.

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